Plant cytogenetics tests can predict toxic effects on human cells: genotoxic and mutagenic effects of Tityus serrulatus scorpion venom on vegetal and human cells

Authors

DOI:

https://doi.org/10.5902/2179460X66067

Keywords:

Cytogenotoxicity, mutagenic action, tunel, comet assay, micronuclei

Abstract

The effects of Tityus serrulatus venom was accessed on the cell cycle and genetic material of the Lactuca sativa L. and compared with the damages to human leukocytes, in order to evaluate the genotoxic and mutagenic potential of toxins on cell types very different. The occurrence of cell cycle alterations and DNA fragmentation was evaluated in Lactuca sativa. Incubations of venom with human leukocytes were also held with subsequent evaluation of cell proliferation index, micronucleus and fragmented DNA. The T. serrulatus venom showed cytogenotoxic, reducing mitotic index and induced alterations in the cell cycle and micronuclei formation. The occurrence of cell death was evidenced by the detection of condensed nuclei, positive TUNEL signals, and presence of DNA fragmentation on lettuce cells. The scorpion venom induced DNA fragmentation and micronuclei in leukocytes. Further, the role of peptides and proteases from this venom in inducing the observed damage was discussed.

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Author Biographies

Silvana Marcussi, Universidade Federal de Lavras

Licenciada em Biologia pela Organização Educacional Barão de Mauá (2001), mestre em Biotecnologia pela UNAERP (2003) e doutora em ciências pela FMRP-USP (Departamento de Bioquímica e Imunologia). Pós-doutora em Farmacologia pela FCFRP-USP (Departamento de análises Clínicas, Toxicológicas e Bromatológicas). Tenho experiência nas áreas de Bioquímica, Toxicologia, Citogenética e Farmacologia atuando principalmente nas subárea de toxinologia e produtos naturais: caracterização enzimática, farmacológica e toxicológica de proteínas de peçonhas de animais; plantas medicinais; inibidores enzimáticos, etc. Coordenadora Adjunto do programa de pós graduação em Agroquímica de 2016 a 2017. Atual Profa. Associada IV na Universidade Federal de Lavras, UFLA-MG (início em 2009), locada no Departamento de Química.

Marcel José Palmieri, Universidade Federal de Lavras

Biólogo, mestre e doutor em Genética e Melhoramento de plantas pela Universidade Federal de Lavras (UFLA). Atualmente é pesquisador atuando na área de prospecção de efeitos tóxicos de compostos químicos e biológicos.

Larissa Fonseca Andrade-Vieira, Universidade Federal de Lavras

Bióloga, phD em Ecotoxicologia pela Université de Lorraine, França. Professora Adjunta do departamento de Biologia da Universidade Federal de Lavras (UFLA). Docente e Orientadora do Programa de Pós Graduação em Botânica Aplicada da UFLA. Atua na área de eco(geno)toxidade de poluentes ambientais com projetos conduzidos dentro da tematica "Prospecção de Efeitos Biológicos". Durante o seu mestrado trabalhou com ênfase em citotoxicidade e genotoxicidade de substâncias químicas no ciclo celular. No doutorado atuou com ênfase em citogenética molecular de forrageiras, tendo auxiliado na implementação das técnicas de Citogenética Molecular (FISH e GISH) no Laboratório de Citogenética da UFLA. Como treinamento pos-doutoral realizou ensaios em organismos modelos para ecotoxicologia aquatica conduzindo testes com padronização ISO para acessar a ecotoxicidade de herbicidas. Atualmente tem trabalhado com o modelo vegetal Lactuca sativa para fins de avaliações de toxidade de poluentes ambientais, com ênfase no resíduo da indústria de alumínio, SPL, em agrotóxicos e produtos naturais.

Amanda Ribeiro Barroso, Universidade Federal de Lavras

Graduada em Biologia pela Universidade Federal de Lavras (UFLA). Mestre em Farmacologia pela Universidade Federal do Paraná (UFPR). Possui experiência na área de Toxicologia e Farmacologia.

 

Mariana Aparecida Braga, Universidade Federal de Lavras

Possui graduação em Licenciatura Plena em Química pela Universidade Federal de Lavras (2012). Mestre em Agroquímica, área de concentração em Química/ Bioquímica (2015). Doutora em Agroquímica área de concentração Química/Bioquímica (UFLA). Tem experiência na área de Química, com ênfase em Bioquímica, enzimologia, atuando principalmente nos seguintes temas: tratamento pós-colheita de frutos, plantas medicinais, tratamento da obesidade, determinação de genotoxicidade e mutagenicidade em plantas medicinais, fitoterápicos, inibidores de enzimas digestivas, farmacologia de proteínas de peçonhas de serpentes, plantas antiofídicas e ministração de aulas práticas para graduação.

Marcus Vinicius Cardoso Trento, Universidade Federal de Lavras

Doutorando em Agroquímica (Química e Bioquímica) na Universidade Federal de Lavras (UFLA). Formado em Ciências Biológicas (Bacharelado) e Mestre em Agroquimica (Quimica e Bioquímica de Produtos Naturais e Sintéticos), ambos pela UFLA. Tem experiência na área de Bioquímica, com ênfase em Toxinologia. Participou do programa Ciência Sem Fronteiras na University of The Fraser Valley em Abbostsford, BC, Canadá.

References

ABDEL-RAHMAN, M. A.; QUINTERO-HERNÁNDEZ, V.; POSSANI, L. D. Scorpion venom gland transcriptomics and proteomics: An Overview. In: GOPALAKRISHNAKONE, P.; CALVETE, J. (eds). Venom Genomics and Proteomics. Dordrecht: Springer, 2016. p. 1-17. DOI: https://doi.org/10.1007/978-94-007-6649-5_29-1

ANDRADE-VIEIRA, L. F.; BOTELHO, C. M.; LAVIOLA, B. G.; PALMIERI, M. J.; PAÇA-FONTES, M. M. Effects of Jatropha curcas oil in Lactuca sativa root tip bioassays. An Acad Bras Cienc., [s.l]. v. 86, n. 1, p. 373–382, 2014. DOI: https://doi.org/10.1590/0001-3765201420130041

ANDRADE-VIEIRA, L. F.; GEDRAITE. L. S.; CAMPOS, J. M. S.; DAVIDE, L. C. Spent Pot Liner (SPL) induced DNA damage and nuclear alterations in root tip cells of Allium cepa as a consequence of programmed cell death. Ecotoxicol Environ Saf., [s.l.], v. 74, n. 4, 882–888, 2011. DOI: https://doi.org/10.1016/j.ecoenv.2010.12.010

ANDRADE-VIEIRA, L. F.; PALMIERI, M. J.; BOTELHO, C. M.; LUBER, J.; SILVA, M. F. F. Evaluation of the antimutagenic potential of Psidium guajava L. extracts via plant bioassays. South A J Botany, [s.l.], v. 113, p. 443–448, 2017. DOI: https://doi.org/10.1016/j.sajb.2017.10.002

CERNI, F. A.; PUCCA, M. B.; ZOCCAL, K. F.; FRANTZ, F. G.; FACCIOLI, L. H.; ARANTES, E. C. Expanding biological activities of Ts19 Frag-II toxin: Insights into IL-17 production. Toxicon, [s.l.], v. 134, p. 18-25, Aug. 2017. DOI: https://doi.org/10.1016/j.toxicon.2017.05.013

COLLINS, A. R.; DUTHIE, S. J.; DOBSON, V. L. Direct enzymic detection of endogenous oxidative base damage in human lymphocyte DNA. Carcinogenesis, [s.l.], v. 14, n. 9, p. 1733–1735, 1993. DOI: https://doi.org/10.1093/carcin/14.9.1733

COLLINS, A. R. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol. Biotechnol., [s.l.], v. 26, n. 3, p. 249–261, 2004. DOI: https://doi.org/10.1385/MB:26:3:249

COLOGNA, C. T.; MARCUSSI, S.; GIGLIO, J. R.; SOARES, A. M.; ARANTES, E. C. Tityus serrulatus scorpion venom and toxins: an overview. Protein Pept Lett., [s.l.], v.16, n. 8, p. 920–932, 2009. DOI: https://doi.org/10.2174/092986609788923329

CUPO, P. Clinical update on scorpion envenoming. Rev. Soc. Bras. Med. Trop., [s.l.], v. 48, n. 6, p. 642-649, 2015. DOI: https://doi.org/10.1590/0037-8682-0237-2015

DONG, Y.; ZHANG, J. Testing the genotoxicity of coking wastewater using Vicia faba and Hordeum vulgare bioassays. Ecotoxicol Environ Saf., [s.l.], v. 73, n. 5, p. 944–948, 2010. DOI: https://doi.org/10.1016/j.ecoenv.2009.12.026

DOYLE, J. J.; DOYLE, J. L. A rapid DNA isolation procedure for small quantities of fresh leaf tissue. Phytochem Bull., [s.l.], v. 19, n. 1, p.11–15, 1987.

FENECH, M.; MORLEY, A. A. Measurement of micronuclei in lymphocytes. Mutat Res Mutagen Relat Subj., [s.l.]. v. 147, p. 29–36, 1985. DOI: https://doi.org/10.1016/0165-1161(85)90015-9

FENECH, M. The in vitro micronucleus technique. Mutat Res - Fundam Mol Mech Mutagen., [s.l.], v. 455, n. 1-2, p. 81–95, 2000. DOI: https://doi.org/10.1016/S0027-5107(00)00065-8

FISKESJÖ, G. The Allium test as a standard in environmental monitoring. Hereditas., [s.l.], v. 102, n. 1, p. 99–112, 1985. DOI: https://doi.org/10.1111/j.1601-5223.1985.tb00471.x

FISKESJÖ, G. The Allium test - an alternative in environmental studies: the relative toxicity of metal ions. Mutat Res - Fundam Mol Mech Mutagen., [s.l.], v. 197, n. 2, p. 243–260, 1988. DOI: https://doi.org/10.1016/0027-5107(88)90096-6

GAJSKI, G.; GARAJ-VRHOVAC. V. Genotoxic potential of bee venom (Apis Mellifera) on human peripheral blood lymphocytes in vitro using single cell gel electrophoresis assay. J Environ Sci Heal Part A., [s.l.], v. 43, p. 1279–1287, 2008. DOI: https://doi.org/10.1080/10934520802177862

GALVANI, N. C.; VILELA, T. C.; DOMINGOS, A. C.; FAGUNDES, M. Í.; BOSA, L. M.; DELLA VECHIA, I. C.; SCUSSEL, R.; PEREIRA, M.; STEINER, B. T.; DAMIANI, A. P.; CHÁVEZ-OLÓRTEGUI, C.; ANDRADE, V. M.; ÁVILA, R. A. M. Genotoxicity evaluation induced by Tityus serrulatus scorpion venom in mice. Toxicon. [s.l.], v. 140, p. 132-138, 2017. DOI: https://doi.org/10.1016/j.toxicon.2017.10.024

GRANT, W. F. Higher plant assays for the detection of chromosomal aberrations and gene mutations - a brief historical background on their use for screening and monitoring environmental chemicals. Mutat Res., [s.l.], v. 426, p. 107–112, 1999. DOI: https://doi.org/10.1016/S0027-5107(99)00050-0

GRANT, W. F.; OWENS, E. T. Zea mays assays of chemical/radiation genotoxicity for the study of environmental mutagens. Mutat Res., [s.l.], v. 613, p. 17–64, 2006. DOI: https://doi.org/10.1016/j.mrrev.2006.04.002

GUPTA, S. DEBNATH, A.; SAHA, A.; GIRI, B.; TRIPATHI, G.; VEDASIROMONI, J. R.; GOMES, A.; GOMES, A. INDIAN black scorpion (Heterometrus bengalensis Koch) venom induced antiproliferative and apoptogenic activity against human leukemic cell lines U937 and K562. Leuk Res., [s.l.], v. 31, p. 817–825, 2007. DOI: https://doi.org/10.1016/j.leukres.2006.06.004

HARA, R. V.; MARIN-MORALES, M. A. In vitro and in vivo investigation of the genotoxic potential of waters from rivers under the influence of a petroleum refinery (São Paulo State - Brazil). Chemosph., [s.l.], v. 174, p. 321-330, 2017. DOI: https://doi.org/10.1016/j.chemosphere.2017.01.142

HARVEY, A. L. Toxins and drug discovery. Toxicon., [s.l.], v. 92, p. 193–200, 2014. DOI: https://doi.org/10.1016/j.toxicon.2014.10.020

HOUSLEY, D. M.; HOUSLEY, G. D.; LIDDELL, M. J.; JENNINGS, E. A. Scorpion toxin peptide action at the ion channel subunit level. Neuropharm., [s.l.], v. 127, p. 46-78, 2017. DOI: https://doi.org/10.1016/j.neuropharm.2016.10.004

KANG, T. S.; GEORGIEVA, D.; GENOV, N.; MURAKAMI, M. T.; SINHA, M.; KUMAR, R. P.; DEY, S.; SHARMA, S.; VRIELINK, A.; BETZEL, C.; TAKEDA, S.; ARNI, R. K.; SINGH, T. P.; KINI, R. M. Enzymatic toxins from snake venom: Structural characterization and mechanism of catalysis. FEBS J., [s.l.], v. 278, p. 4544–4576, 2011. DOI: https://doi.org/10.1111/j.1742-4658.2011.08115.x

KIRSCH-VOLDERS, M. Towards a validation of the micronucleus test. Mutat Res., [s.l.], v. 392, p. 1-4, 1997. DOI: https://doi.org/10.1016/S0165-1218(97)00039-6

KOH, C. Y.; KINI, R. M. From snake venom toxins to therapeutics - Cardiovascular examples. Toxicon., [s.l.], v. 59, n° 4, p. 497–506, 2012. DOI: https://doi.org/10.1016/j.toxicon.2011.03.017

LEBAUDY, A.; VÉRY, A. A.; SENTENAC, H. K+ channel activity in plants: Genes, regulations and functions. FEBS L., [s.l.], v. 581, p. 2357–2366, 2007. DOI: https://doi.org/10.1016/j.febslet.2007.03.058

LEE, Y. J.; KANG, S. J.; KIM, B. M.; KIM, Y. J.; WOO, H. D.; CHUNG, H. W. Cytotoxicity of honeybee (Apis mellifera) venom in normal human lymphocytes and HL-60 cells. Chem Biol Interact., [s.l.], v. 169, p. 189–197, 2007. DOI: https://doi.org/10.1016/j.cbi.2007.06.036

LEME, D. M.; MARIN-MORALES, M. A. Allium cepa test in environmental monitoring: A review on its application. Mutat Res - Rev Mutat Res., [s.l.], v. 682, p. 71–81, 2009. DOI: https://doi.org/10.1016/j.mrrev.2009.06.002

LOWE, R. M.; FARRELL, P. M. A portable device for the electrical extraction of scorpion venom. Toxicon., [s.l.], v. 57, p. 244-247, 2011. DOI: https://doi.org/10.1016/j.toxicon.2010.11.017

MARCUSSI, S.; SANTOS, P. R. S.; MENALDO, D. L.; SILVEIRA, L. B.; SANTOS-FILHO, N. A.; MAZZI, M. V.; SILVA, S. L.; STÁBELI, R. G.; ANTUNES, L. M. G.; SOARES, A. M. Evaluation of the genotoxicity of Crotalus durissus terrificus snake venom and its isolated toxins on human lymphocytes. Mutat Res - Genet Toxicol Environ Mutagen., [s.l.], v. 724, p. 59–63, 2011. DOI: https://doi.org/10.1016/j.mrgentox.2011.06.004

MARCUSSI, S.; STÁBELI, R. G.; SANTOS-FILHO, N. A.; MENALDO, D. L.; PEREIRA, L. L. S.; ZULIANI, J. P.; CALDERON, L. A.; SILVA, S. L.; ANTUNES, L. M. G.; SOARES, A. M. Genotoxic effect of Bothrops snake venoms and isolated toxins on human lymphocyte DNA. Toxicon., [s.l.], v. 65, p. 9–14, 2013. DOI: https://doi.org/10.1016/j.toxicon.2012.12.020

OLIVEIRA-MENDES, B. B. R.; MIRANDA, S. E. M.; SALES-MEDINA, D. F.; MAGALHÃES, B. F.; KALAPOTHAKIS, Y.; SOUZA, R. P.; CARDOSO, V. N.; BARROS, A. L. B.; GUERRA-DUARTE, C.; KALAPOTHAKIS, E.; HORTA, C. C. R. Inhibition of Tityus serrulatus venom hyaluronidase affects venom biodistribution. PLoS Negl Trop Dis., [s.l.], v. 13, e0007048, 19 April, 2019. DOI: https://doi.org/10.1371/journal.pntd.0007048

PALMIERI, M. J.; ANDRADE-VIEIRA, L. F.; CAMPOS, J. M. S.; GEDRAITE, L. S.; DAVIDE , L. C. Cytotoxicity of Spent Pot Lineron Allium cepa root tip cells: A comparative analysis in meristematic cell type on toxicity bioassays. Ecotoxicol Environ Saf., [s.l], v. 133, p. 442-447, 2016b. DOI: https://doi.org/10.1016/j.ecoenv.2016.07.016

PALMIERI, M. J.; ANDRADE-VIEIRA, L. F.; TRENTO, M. V. C.; ELEUTÉRIO, M. W. F.; LUBER, J.; DAVIDE, L.; MARCUSSI, S. Cytogenotoxic effects of Spent Pot Liner (SPL) and its main components on human leukocytes and meristematic cells of Allium cepa. Water Air Soil Pollut., [s.l.], v. 227, p. 156-166, 2016a. DOI: https://doi.org/10.1007/s11270-016-2809-z

PALMIERI, M. J. LACTUCA SATIVA: BIOINDICADOR PARA ANÁLISE DO EFEITO GENOTÓXICO DE PEÇONHAS. Doctorade—[s.l.] Universidade Federal de Lavras (UFLA), 2016.

PALMIERI, M. J.; BARROSO, A. R.; ANDRADE-VIEIRA, L. F.; MONTEIRO, M. C.; SOARES, A. M.; CESAR, P. H. S.; BRAGA, M. A.; TRENTO, M. V. C.; MARCUSSI, S.; DAVIDE, L. C. Polybia occidentalis and Polybia fastidiosa venom: a cytogenotoxic approach of effects on human and vegetal cells. Drug Chem Toxicol., [s.l.], v. 44, p. 1-9, 2019. DOI: https://doi.org/10.1080/01480545.2019.1631339

PUCCA, M. B.; CERNI, F. A.; PINHEIRO-JUNIOR, E. L.; ZOCCAL, K. F.; BORDON, K. C. F.; AMORIM, F. G.; PEIGNEUR, S.; VRIENS, K.; THEVISSEN, K.; CAMMUE, B. P. A.; MARTINS JÚNIOR, R. B.; ARRUDA, E.; FACCIOLI, L. H.; TYTGAT, J.; ARANTES, E. C. Non-disulfide-bridged peptides from Tityus serrulatus venom: Evidence for proline-free ACE-inhibitors. Peptides., [s.l.], v. 82, p. 44-51, 2016. DOI: https://doi.org/10.1016/j.peptides.2016.05.008

R DEVELOPMENT CORE TEAM. R: A Language and Environment for Statistical Computing. Viena R Found Stat Comput. 2015.

RECKZIEGEL, G. C.; PINTO, J. R. V. L. Scorpionismo in Brazil in the years 2000 to 2012. J. Venom Anim. Toxins Incl. Trop. Dis., [s.l.], v. 20, p. 46-54, 2014. DOI: https://doi.org/10.1186/1678-9199-20-46

REIS, G. B. D.; ANDRADE-VIEIRA, L. F.; MORAES, I. C.; CESAR, P. H. S.; MARCUSSI, S.; DAVIDE, L. C. Reliability of plant root comet assay in comparison with human leukocyte comet assay for assessment environmental genotoxic agents. Ecotoxicol Environ Saf., [s.l.], v. 142, p. 110-116, 2017. DOI: https://doi.org/10.1016/j.ecoenv.2017.04.004

SANTOS, F. E.; CARVALHO, M. S. S.; SILVEIRA, G. L.; CORREA, F. F.; CARDOSO, M. D. G.; ANDRADE-VIEIRA, L. F.; VILELA, L. R. Phytotoxicity and cytogenotoxicity of hydroalcoholic extracts from Solanum muricatum Ait. and Solanum betaceum Cav. (Solanaceae) in the plant model Lactuca sativa. Environ Sci Pollut Res., [s.l.], v. 25, p. 1-11, 2018.

SILVA, M. A.; SOUZA, T. G.; MELO, M. E. G.; SILVA, J. M.; LIMA, J. R.; LIRA, A. F. A.; AGUIAR-JÚNIOR, F. C. A.; MARTINS, R. D.; JORGE, R. J. B.; CHAGAS, C. A.; TEIXEIRA, V. W.; TEIXEIRA, A. A. C. Tityus stigmurus venom causes genetic damage in blood and testicular cells and affects the number and morphology of gametogenic lineage cells in mice. Toxicon., [s.l.], v. 185, p. 114-119, 2020. DOI: https://doi.org/10.1016/j.toxicon.2020.07.006

SINGH, N. P.; MCCOY, M. T.; TICE, R. R.; SCHNEIDER, E. L. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res., [s.l.], v. 175, p. 184–191, 1988. DOI: https://doi.org/10.1016/0014-4827(88)90265-0

ÜSTÜN, S.; HAFRÉN, A.; HOFIUS, D. Autophagy as a mediator of life and death in plants. Curr Opin Plant Biol., [s.l.], v. 40, p. 122-130, 2017. DOI: https://doi.org/10.1016/j.pbi.2017.08.011

ZAMBELLI, V. O.; PASQUALOTO, K. F.; PICOLO, G.; CHUDZINSKI-TAVASSI, A. M.; CURY, Y. Harnessin the knowledge of animal toxins to generate drugs. Pharmacol Res., [s.l.], v. 112, p. 30-36, 2016. DOI: https://doi.org/10.1016/j.phrs.2016.01.009

ZARGAN, J.; SAJAD, M.; UMAR, S.; NAIME, M.; ALI, S.; KHAN, H. A. Scorpion (Androctonus crassicauda) venom limits growth of transformed cells (SH-SY5Y and MCF-7) by cytotoxicity and cell cycle arrest. Exp Mol Pathol., [s.l.], v. 91, p. 447–454, 2011. DOI: https://doi.org/10.1016/j.yexmp.2011.04.008

ZHOUA, S.; HONG, Q.; LI, Y.; LI. Q. Wang M. Autophagy contributes to regulate the ROS levels and PCD progress in TMV infected tomatoes. Plant Sci., [s.l.], v. 269, p. 12–19, 2018. DOI: https://doi.org/10.1016/j.plantsci.2017.11.002

ZOCCAL, K. F.; BITENCOURT, C. S.; SORGI, C. A.; BORDON, K. C. F.; SAMPAIO, S. V.; ARANTES, E. C.; FACCIOLI, L. H. Ts6 and Ts2 from Tityus serrulatus venom induce inflammation by mechanisms dependent on lipid mediators and cytokine production. Toxicon., [s.l.], v. 61, p. 1–10, 2013. DOI: https://doi.org/10.1016/j.toxicon.2012.10.002

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2023-10-11

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Marcussi, S., Palmieri, M. J., Andrade-Vieira, L. F., Barroso, A. R., Braga, M. A., & Trento, M. V. C. (2023). Plant cytogenetics tests can predict toxic effects on human cells: genotoxic and mutagenic effects of Tityus serrulatus scorpion venom on vegetal and human cells. Ciência E Natura, 45, e19. https://doi.org/10.5902/2179460X66067

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Vol. 45 (2023): Continuous Publication

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Biology-Genetics

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